Carbon monoxide (CO) gas is poisonous in high concentrations. However, it is now recognized as an important signaling molecule (Verma et al., Science 259:381-384, 1993). It has also been suggested that carbon monoxide acts as a neuronal messenger molecule in the brain (Id.) and as a neuro-endocrine modulator in the hypothalamus (Pozzoli et al., Endocrinology 735:2314-2317, 1994). Like nitric oxide (NO), carbon monoxide is a smooth muscle relaxant (Utz et al., Biochem Pharmacol. 47:195-201, 1991; Christodoulides et al., Circulation 97:2306-9, 1995) and inhibits platelet aggregation (Mansouri et al, Thromb Haemost. 48:286-8, 1982). Inhalation of low levels of carbon monoxide has been shown to have anti-inflammatory effects in some models.
Ileus is a condition characterized by a lack of bowel motility, and is one of the more common forms of intestinal obstruction (see, e.g., Oxford Textbook of Surgery, Morris and Malt, Eds., Oxford University Press (1994)). Often, ileus occurs throughout the intestinal tract (e.g., both large and small bowel), but it can sometimes involve only one or several segments thereof. Intestinal manipulation during abdominal surgery frequently leads to ileus.
Various pharmaceutical approaches to treating ileus have been proposed (see, e.g., U.S. Pat. No. 5,362,756 (fedotozine); U.S. Pat. No. 5,929,035 (neuropeptides); U.S. Pat. No. 6,214,843 (pyrazolopyridine); and U.S. Pat. No. 5,958,407 (e.g., antagonizing proteinase-activated receptor-2)).